Research carried out at Wayne State and Duke University Schools of Medicine has identified 26 unique genetic variants in Black men that appear to be associated with more severe prostate cancer in this population group.
Prostate cancer is the most common cancer diagnosed in adult men in the U.S. Although it has a high survival rate, with an average 15-year survival rate of around 95%, there are still 248,530 cases per year and it ranks second in overall cancer mortality for adult men causing almost 35,000 deaths per year.
Black men have a higher incidence and are more than twice as likely to die from prostate cancer compared with non-Hispanic White men. This is thought to be partly due to societal causes, but could also at least partly be explained by genetic variants that are more common in Black than non-Hispanic White men.
“We need to take a closer look at genetic associations to learn more about the susceptibility Black men have to developing prostate cancer,” said co-lead investigator Kathleen Cooney, a professor at Duke University, in a press statement. “This could potentially reduce health disparities.”
Until recently, many genetic studies were unfortunately dominated by non-Hispanic White participants and so knowledge about pathogenic (P) or likely pathogenic (LP) variants linked to prostate cancer in Black populations was limited.
To explore this in more depth, Cooney and colleagues sequenced germline exomic DNA from 743 Black men with a diagnosis of prostate cancer who were 62 years old or younger.
Writing in JCO Precision Oncology, the researchers report finding 26 unique variants (P/LP) in 14 genes. These included HOXB13, BRCA1/2, BRIP1, ATM, CHEK2, and PALB2, among others. These variants were rare and only found in 30 men (4%) in the group. They also found 33 genetic variants of unknown significance, in 16 genes across 39 men.
The men who carried the risk variants were more likely to have higher prostate-specific antigen at diagnosis than non-carriers, and be diagnosed with metastatic disease. These men were also more likely to have a first degree relative with a form of DNA damage repair (DDR) gene-associated cancer than non-carriers.
“Genetic variation in DNA damage repair genes and HOXB13 may be an important risk factor for Black men diagnosed with early-onset prostate cancer,” write the authors.
“Further investigation of these genetic associations will provide insight into the unique susceptibility Black men have to developing prostate cancer, potentially reducing current health disparities.”
